Cd14⁺ suppressor cells in cytokine mobilized stem cell products

Forty percent of the cells within GM-CSF mobilized peripheral stem cell products (PSC) ire CD14⁺ which following isolation are directly associated with a suppressor cell function. These cells suppress T cell responses to PHA, pokeweed mitogen, IL-2 and IL-12. However, their removal from PSC products restores T cell function and proliferative capacity. The suppressor cells are low density, adherent and phagocytic; in addition to HLA-DR⁺, CD4⁺, CD11a⁺, CD11b⁺, CD86 (B7.2)⁺, CD80 (B7.1)^-, CD16^- and CD1a^- suggesting that they are either monocyte or monocyte-dendritic cell precursors. Following 7 days of incubation with TNF and GM-CSF, cells remain CD14⁺CD1a^- but go from CD86⁺ to CD80⁺ while retaining suppressor cell activity suggesting a true monocytic origin. Cell-cell contact is required for suppression (paraformaldehyde treated CD14 cells are suppressive) and is not neutralized by antibodies directed against TNF. The PSC products have increased mRNA levels for IL-10, IL-4, IL-8, IL-2, TNF and IFN-γ compared to normal PBL; although the IL-10 is associated with CD14⁺ and not T cells. The suppressor cell activity has potential to regulate immune recovery following myeloablative therapy and the removal of these cells from the PSC has therapeutic potential. Further, they may reduce immunologie and therapeutic responses to adjuvant immunotherapy, conversely, suppressor cells have clinical potential for allogeneic graft-versushost disease or solid organ graft rejection.